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PDBsum entry 4p5t
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Immune system
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PDB id
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4p5t
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Contents |
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197 a.a.
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238 a.a.
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179 a.a.
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199 a.a.
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References listed in PDB file
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Key reference
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Title
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Effect of cdr3 sequences and distal V gene residues in regulating tcr-Mhc contacts and ligand specificity.
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Authors
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B.D.Stadinski,
P.Trenh,
B.Duke,
P.G.Huseby,
G.Li,
L.J.Stern,
E.S.Huseby.
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Ref.
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J Immunol, 2014,
192,
6071-6082.
[DOI no: ]
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PubMed id
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Abstract
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The mature T cell repertoire has the ability to orchestrate immunity to a wide
range of potential pathogen challenges. This ability stems from thymic
development producing individual T cell clonotypes that express TCRs with unique
patterns of Ag reactivity. The Ag specificity of TCRs is created from the
combinatorial pairing of one of a set of germline encoded TCR Vα and Vβ gene
segments with randomly created CDR3 sequences. How the amalgamation of germline
encoded and randomly created TCR sequences results in Ag receptors with unique
patterns of ligand specificity is not fully understood. Using cellular,
biophysical, and structural analyses, we show that CDR3α residues can modulate
the geometry in which TCRs bind peptide-MHC (pMHC), governing whether and how
germline encoded TCR Vα and Vβ residues interact with MHC. In addition, a
CDR1α residue that is positioned distal to the TCR-pMHC binding interface is
shown to contribute to the peptide specificity of T cells. These findings
demonstrate that the specificity of individual T cell clonotypes arises not only
from TCR residues that create direct contacts with the pMHC, but also from a
collection of indirect effects that modulate how TCR residues are used to bind
pMHC.
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